For our last issue, HIVandHepatitis.com reviews some the year's major HIV, viral hepatitis, and related news highlights. As we enter 2018, antiretroviral treatment for HIV is about as good as it can get, use of PrEP for HIV prevention is expanding rapidly, and most people can be cured of hepatitis C with 2 or 3 months of well-tolerated therapy. But these advances are still not reaching everyone who needs them. The search for a functional cure for HIV, better treatments for hepatitis B, and management of fatty liver disease remain major challenges for the year ahead.

1. Convergence of HIV Cure and Cancer Research

Several therapies used to treat cancer are finding a new role in HIV cure studies, while discoveries by HIV cure researchers about how the immune system works are aiding the development of novel immunotherapies for cancer. The only known HIV cure to date resulted from a bone marrow transplant for leukemia. Recognizing this convergence, the International AIDS Society held the first HIV Cure and Cancer Forum(formerly known as the Towards an HIV Cure Symposium) preceding the International AIDS Society Conference on HIV Science this summer in Paris. So far, much of the joint research is highlighting why it is so difficult to cure both diseases.

2. Undetectable = Untransmittable

Increasing evidence that HIV-positive people on antiretroviral therapy (ART) with undetectable viral load do not transmit the virus has been a top story for a few years, but in 2017 "U=U" hit the mainstream. The latest results come from the Opposites Attract study, which saw no cases of HIV transmission within serodiscordant gay male couples when the HIV-positive partner was on treatment with fully suppressed viral load. The U.S. Centers for Disease Control and Prevention (CDC) acknowledged in October that undetectable equals untransmittable, and a growing movement is getting the word out to the community.

3. Dual-Drug HIV Treatment and Other New Therapies

Research continues to show that people who switch from standard 3-drug antiretroviral therapy to some 2-drug regimens can maintain viral suppression. After the SWORD trials confirmed that the integrase inhibitor dolutegravir plus rilpivirine can maintain an undetectable viral load, the Food and Drug Administration (FDA) approved this combo as the first 2-drug single-tablet regimen, known as Juluca. Next out of the development pipeline are likely to be ibalizumab, a monoclonal antibody entry inhibitor for people with highly resistant HIV and limited existing treatment options, Gilead Science's new integrase inhibitor bictegravir, and perhaps Merck's next-generation NNRTI doravirine.

4. HIV Infections Fall -- But Not for Everyone

The number of annual new HIV infections in the U.S. fell by 18% overall from 2008 to 2014, according to the latest data from the CDC. Heterosexuals and people who inject drugs saw large drops, while the HIV incidence rate remained stable for gay and bisexual men. Within the latter category, declines in some subgroups balances increases in others. Black gay men -- a group that has seen a rising incidence in recent years -- had a stable rate in 2014, but Latino gay men saw an increase. On the local level, San Francisco reported a 16% decline in new infections (similar to last year's drop), London has seen a large drop in new HIV diagnoses at sexual health clinics for gay men, and New York City recently reported that new diagnoses are at an all-time low. Experts attribute the declines to a combination of increased testing, more people starting early antiretroviral treatment, and pre-exposure prophylaxis (PrEP).

5. Trans People and HIV

The HIV community has known for some time that transgender women have a high rate of HIV infection and disproportionately poor outcomes. The same may well be true for trans men, but there isn't enough data. At this year's IAS Conference on HIV Science, researchers presented studies showing that many trans women are hesitant to use antiretroviral therapy due to concerns about interactions with feminizing hormones. Studies are currently underway to learn more about whether hormones interact with HIV treatment or PrEP.

6. New Hepatitis C Approvals -- and the End of Drug Development?

This year the Food and Drug Administration approved 2 new combination pills that work against all hepatitis C virus (HCV) genotypes. AbbVie's Mavyretis a fixed-dose coformulation containing the HCV protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir. Treatment duration for previously untreated people is 8 weeks for those without cirrhosis and 12 weeks for those with compensated cirrhosis. Gilead Science's Vosevi contains the HCV NS5B polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir. It was approved as "salvage therapy" for people who were not cured with previous direct-acting antivirals. Contemporary regimens have cure rates approaching 100%, leading some experts to question whether hepatitis C drug development is coming to an end. Both Merck and Janssen recently announced that they are halting development of promising HCV therapies.

7. Can Hepatitis C Be Eliminated

Given the high cure rates of the latest treatments, researchers and advocates are asking whether hepatitis C can be eliminated as a public health threat. Small studies have shown that expanding treatment can reduce new infections within certain populations, including gay and bisexual men in the Netherlands. Eliminating HCV as a global public health concern is feasible, but to do so more people have to be tested and treated and prices of direct-acting antivirals need to come down, according to presentations at the AASLD Liver Meeting and the World Hepatitis Summit. Currently 9 countries are on track to eliminate hepatitis C, 22 are working towards elimination, and more than 60 will not be able to eliminate HCV given their current policies. In the U.S., even as more of the traditional "baby boomer" population are treated and cured, HCV infection is rising steeply among younger people in association with the burgeoning opioid epidemic, according to the CDC.

8. Hepatitis C Treatment and Liver Cancer

In 2016, researchers presented some data suggesting that people cured of hepatitis C with new direct-acting antivirals (DAAs) might be more likely to develop hepatocellular carcinoma (HCC) than those treated with interferon. But this year studies provided ample reassurance that this is not the case. At the EASL International Liver Congress, researchers presented data from a meta-analysis of more than 40 studies showing that people treated with DAAs do not have a higher likelihood of developing liver cancer. Indeed, a large study of U.S. veterans presented at the AASLD Liver Meeting showed that curing hepatitis C -- with either type of treatment -- reduces liver cancer risk by about 70%.

9. Progress on Hepatitis B

In contrast with hepatitis C, hepatitis B remains difficult to cure. Nucleoside/nucleotide antivirals like tenofovir (Viread or Vemlidy) can suppress HBV replication over the long term, but they usually do not lead to a cure, as indicated by loss of hepatitis B surface antigen (HBsAg). Researchers are exploring several approaches that target different steps of the hepatitis B virus (HBV) lifecycle, including the immune-modulating drug inarigivir (SB 9200), the nucleic acid polymer REP 2139, the RNA interference therapy ARB-1467, and the capsid assembly inhibitor JNJ-56136379.

10. Fatty Liver Disease a Growing Challenge

Progress has been slow in finding treatments for non-alcoholic fatty liver disease (NALFD) and its more severe form, non-alcoholic steatosis (NASH). As an effective vaccine reduces new hepatitis B infections, contemporary treatments easily cure hepatitis C, and the population grows more obese, fatty liver disease has become a leading cause of liver disease worldwide. There are currently no approved therapies, but researchers reported this year that theacetyl-CoA carboxylase inhibitor GS-0976 reduced liver fat accumulation and fibrosis in people with NASH in a Phase 2 study. In the meantime, as this and other candidates make their way through the development pipeline, a healthy diet and exercise have been shown to improve fatty liver disease.